WOODCLIFF LAKE, N.J., Oct. 28, 2016 /PRNewswire/ -- Eisai Inc. announced today the initiation of two multi-center, global Phase 3 clinical trials assessing FYCOMPA® (perampanel) CIII in two different patient populations: patients age 2 years and above with inadequately controlled seizures associated with Lennox-Gastaut Syndrome (LGS) (Study 338), a rare and often debilitating form of childhood-onset epilepsy, and in children ages 4 through 11 years with inadequately controlled partial-onset seizures (POS) (Study 311).
FYCOMPA is indicated as an adjunctive therapy for the treatment of POS with or without secondarily generalized seizures and primary generalized tonic-clonic seizures in patients with epilepsy who are 12 years of age and older. FYCOMPA is not indicated for LGS, or for patients younger than 12. Please see Important Safety Information for FYCOMPA, including Boxed WARNING for Serious Psychiatric and Behavioral Reactions, below.
"We are committed to helping the epilepsy community through the continued development of options that may address unmet medical needs," said Lynn Kramer, M.D., Chief Clinical Officer and Chief Medical Officer, Neurology Business Group, Eisai. "Through the initiation of these two clinical trials – one that looks at the pediatric population and the other involving those with LGS – we hope to demonstrate the value of perampanel for a broader range of patients who suffer from these conditions."
Study 311 is the first pivotal study to follow the November 2015 FDA communication to sponsors that allowed companies "to extrapolate to pediatric patients 4 years of age and older the effectiveness of drugs approved for the treatment of partial-onset seizures (POS) in adults." Under this policy, drug manufacturers must also provide long-term, open-label safety data in patients 4 years and older, the data that Study 311 is designed to provide.
Patients and investigators interested in participating in either trial should contact Eisai Medical Information at 1-888-274-2378.
This release discusses investigational uses for an FDA-approved product. It is not intended to convey conclusions about efficacy or safety. There is no guarantee that any investigational uses of such product will successfully complete clinical development or gain FDA approval.
About Study 338 (Evaluating perampanel in Patients with LGS)
The primary objective of Study 338, a double-blind, randomized, placebo-controlled trial with an open-label extension, will be to evaluate whether perampanel, when given as adjunctive antiepileptic treatment, is superior to placebo in reducing the number of drop seizures in participants at least 2 years of age with inadequately controlled seizures associated with LGS. Key secondary objectives include evaluating whether perampanel given as adjunctive antiepileptic treatment is superior to placebo in reducing the incidence of all seizures in study subjects; and evaluating whether perampanel given as adjunctive antiepileptic treatment is superior to placebo in the 50% responder rate for drop seizures, non-drop and total seizures, respectively, in study subjects.
The study will enroll approximately 142 patients receiving 1-3 concomitant antiepileptic drugs (AEDs). Study participants will be randomized to receive perampanel up to 8 mg or placebo in a 1:1 ratio during three periods: titration (6 weeks), maintenance (12 weeks), and follow-up (4 weeks).
About Study 311 (Evaluating perampanel in Children ages 4 through 11)
Study 311 is a global open-label, multicenter trial with an extension phase to evaluate the safety, tolerability and exposure-efficacy relationship of perampanel oral suspension when administered as an adjunctive therapy in children, ages 4 through 11, with inadequately controlled partial-onset seizures or primary generalized tonic-clonic seizures. Study 311 will enroll roughly 160 patients—approximately 120 with partial-onset seizures and 40 with primary generalized tonic-clonic seizures, who will undergo pretreatment and treatment phases, during which they will be administered up to 12 mg of perampanel daily. The primary endpoint will be safety and tolerability, which include incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), laboratory parameters, vital signs, and ECG parameters.
Epilepsy is a medical condition that produces seizures affecting a variety of mental and physical functions. According to the Institute of Medicine, epilepsy is one of the most common neurological disorders, which affects 2.9 million people in the United States. Partial-onset seizures are the most common type of seizure seen in people with epilepsy, accounting for 60 percent of all seizures. Generalized seizures account for approximately 40 percent of all epilepsy, with primary generalized tonic-clonic seizures being one of the most common and severe forms of generalized seizures. Lennox-Gastaut Syndrome is diagnosed in more than 30,000 children and adults in the United States.
About FYCOMPA (perampanel)
FYCOMPA (perampanel) is indicated as adjunctive therapy for the treatment of partial-onset seizures with or without secondarily generalized seizures and primary generalized tonic-clonic seizures in patients with epilepsy 12 years of age and older.
FYCOMPA is an oral medication and is a selective, non-competitive AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor antagonist. The precise mechanism by which FYCOMPA exerts its antiepileptic effects in humans is unknown.
FYCOMPA has been designated by the U.S. Drug Enforcement Administration as a federally-controlled substance (CIII).
Important Safety Information for FYCOMPA (perampanel) CIII
WARNING: SERIOUS PSYCHIATRIC AND BEHAVIORAL REACTIONS
Serious Psychiatric and Behavioral Reactions
In the partial-onset seizures clinical trials, hostility- and aggression-related adverse reactions occurred in 12% and 20% of patients randomized to receive FYCOMPA at doses of 8 mg and 12 mg per day, respectively, compared to 6% of patients in the placebo group. These effects were dose-related and generally appeared within the first 6 weeks of treatment, although new events continued to be observed through more than 37 weeks. These effects in FYCOMPA-treated patients led to dose reduction, interruption, and discontinuation more frequently than placebo-treated patients. The combination of alcohol and FYCOMPA significantly worsened mood and increased anger. Homicidal ideation and/or threat have also been reported postmarketing in patients treated with FYCOMPA. Patients taking FYCOMPA should avoid the use of alcohol. Patients, their caregivers, and families should be informed that FYCOMPA may increase the risk of psychiatric events. Patients should be monitored during treatment and for at least one month after the last dose of FYCOMPA, and especially when taking higher doses and during the initial few weeks of drug therapy (titration period) or at other times of dose increases. Similar serious psychiatric and behavioral events were observed in the primary generalized tonic-clonic (PGTC) seizure clinical trial.
Suicidal Behavior and Ideation
Antiepileptic drugs (AEDs), including FYCOMPA, increase the risk of suicidal thoughts or behavior in patients. Anyone considering prescribing FYCOMPA or any other AED must balance the risk of suicidal thoughts or behavior with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Patients, their caregivers, and families should be informed of the risk and advised to monitor and immediately report the emergence or worsening of depression, suicidal thoughts or behavior, thoughts about self-harm and/or any unusual changes in mood or behavior. Should suicidal thoughts and behavior emerge during treatment, consider whether the emergence of these symptoms in any given patient may be related to the illness being treated.
Dizziness and Gait Disturbance
FYCOMPA caused dose-related increases in events related to dizziness and disturbance in gait or coordination. Dizziness and vertigo were reported in 35% and 47% of patients in the partial-onset seizure trials randomized to receive FYCOMPA at doses of 8 mg and 12 mg per day, respectively, compared to 10% of placebo-treated patients. Gait disturbance related events were reported in 12% and 16% of patients in the partial-onset seizure clinical trials randomized to receive FYCOMPA at doses of 8 mg and 12 mg per day, respectively, compared to 2% of placebo-treated patients. These adverse reactions occurred mostly during the titration phase. These adverse reactions were also observed in the PGTC seizure clinical trial.
Somnolence and Fatigue
FYCOMPA caused dose-dependent increases in somnolence and fatigue-related events. Somnolence was reported in 16% and 18% of patients in the partial-onset seizure trials randomized to receive FYCOMPA at doses of 8 mg and 12 mg per day, respectively, compared to 7% of placebo patients. Fatigue-related events were reported in 12% and 15% of patients in the partial-onset seizure trials randomized to receive FYCOMPA at doses of 8 mg and 12 mg per day, respectively, compared to 5% of placebo patients. These adverse reactions occurred mostly during the titration phase. These adverse reactions were also observed in the PGTC seizure clinical trial. Patients should be advised against engaging in hazardous activities requiring mental alertness, such as operating motor vehicles or dangerous machinery, until the effect of FYCOMPA is known.
Falls were reported in 5% and 10% of patients in the partial-onset seizure clinical trials randomized to receive FYCOMPA at doses of 8 mg and 12 mg per day, respectively, compared to 3% of placebo-treated patients.
Withdrawal of AEDs
A gradual withdrawal is generally recommended with AEDs to minimize the potential of increased seizure frequency, but if withdrawal is a response to adverse events, prompt withdrawal can be considered.
Most Common Adverse Reactions
The most common adverse reactions in patients receiving FYCOMPA (≥5% and ≥1% higher than placebo) include dizziness, somnolence, fatigue, irritability, falls, nausea, weight gain, vertigo, ataxia, headache, vomiting, contusion, abdominal pain, and anxiety.
FYCOMPA may decrease the efficacy of contraceptives containing levonorgestrel. Plasma levels of FYCOMPA were decreased when administered with carbamazepine, phenytoin, or oxcarbazepine. Concomitant use of FYCOMPA with other strong CYP3A inducers (e.g., rifampin, St. John's wort) should be avoided. Multiple dosing of FYCOMPA 12 mg per day enhanced the effects of alcohol on vigilance and alertness, and increased levels of anger, confusion, and depression. These effects may also be seen when FYCOMPA is used in combination with other CNS depressants.
Pregnancy and Lactation
Physicians are advised to recommend that pregnant patients taking FYCOMPA enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry. Caution should be exercised when FYCOMPA is administered to pregnant or nursing women as there are no adequate data on the developmental risk associated with use in pregnant women, and no data on the presence of perampanel in human milk, the effects on the breastfed child, or the effects of the drug on milk production.
Hepatic and Renal Impairment
Use in patients with severe hepatic or severe renal impairment is not recommended. Dosage adjustments are recommended in patients with mild or moderate hepatic impairment. Use with caution in patients with moderate renal impairment.
Drug Abuse and Dependence
FYCOMPA is a Schedule III controlled substance and has the potential to be abused and lead to drug dependence.
Please see accompanying Full Prescribing Information for FYCOMPA (perampanel), including Boxed WARNING.
About Eisai Inc.
At Eisai Inc., human health care (hhc) is our goal. We give our first thoughts to patients and their families, and helping to increase the benefits health care provides. As the U.S. pharmaceutical subsidiary of Tokyo-based Eisai Co., Ltd., we have a passionate commitment to patient care that is the driving force behind our efforts to discover and develop innovative therapies to help address unmet medical needs.
Eisai is a fully integrated pharmaceutical business that operates in two global business groups: oncology and neurology (dementia-related diseases and neurodegenerative diseases). Each group functions as an end-to-end global business with discovery, development, and marketing capabilities. Our U.S. headquarters, commercial and clinical development organizations are located in New Jersey; our discovery labs are in Massachusetts and Pennsylvania; and our global demand chain organization resides in Maryland and North Carolina. To learn more about Eisai Inc., please visit us at www.eisai.com/US.
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